Cargando…

The Effect of Dysfunctional Ubiquitin Enzymes in the Pathogenesis of Most Common Diseases

Ubiquitination is a multi-step enzymatic process that involves the marking of a substrate protein by bonding a ubiquitin and protein for proteolytic degradation mainly via the ubiquitin–proteasome system (UPS). The process is regulated by three main types of enzymes, namely ubiquitin-activating enzy...

Descripción completa

Detalles Bibliográficos
Autores principales: Celebi, Gizem, Kesim, Hale, Ozer, Ebru, Kutlu, Ozlem
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7503467/
https://www.ncbi.nlm.nih.gov/pubmed/32882786
http://dx.doi.org/10.3390/ijms21176335
_version_ 1783584400788684800
author Celebi, Gizem
Kesim, Hale
Ozer, Ebru
Kutlu, Ozlem
author_facet Celebi, Gizem
Kesim, Hale
Ozer, Ebru
Kutlu, Ozlem
author_sort Celebi, Gizem
collection PubMed
description Ubiquitination is a multi-step enzymatic process that involves the marking of a substrate protein by bonding a ubiquitin and protein for proteolytic degradation mainly via the ubiquitin–proteasome system (UPS). The process is regulated by three main types of enzymes, namely ubiquitin-activating enzymes (E1), ubiquitin-conjugating enzymes (E2), and ubiquitin ligases (E3). Under physiological conditions, ubiquitination is highly reversible reaction, and deubiquitinases or deubiquitinating enzymes (DUBs) can reverse the effect of E3 ligases by the removal of ubiquitin from substrate proteins, thus maintaining the protein quality control and homeostasis in the cell. The dysfunction or dysregulation of these multi-step reactions is closely related to pathogenic conditions; therefore, understanding the role of ubiquitination in diseases is highly valuable for therapeutic approaches. In this review, we first provide an overview of the molecular mechanism of ubiquitination and UPS; then, we attempt to summarize the most common diseases affecting the dysfunction or dysregulation of these mechanisms.
format Online
Article
Text
id pubmed-7503467
institution National Center for Biotechnology Information
language English
publishDate 2020
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-75034672020-09-23 The Effect of Dysfunctional Ubiquitin Enzymes in the Pathogenesis of Most Common Diseases Celebi, Gizem Kesim, Hale Ozer, Ebru Kutlu, Ozlem Int J Mol Sci Review Ubiquitination is a multi-step enzymatic process that involves the marking of a substrate protein by bonding a ubiquitin and protein for proteolytic degradation mainly via the ubiquitin–proteasome system (UPS). The process is regulated by three main types of enzymes, namely ubiquitin-activating enzymes (E1), ubiquitin-conjugating enzymes (E2), and ubiquitin ligases (E3). Under physiological conditions, ubiquitination is highly reversible reaction, and deubiquitinases or deubiquitinating enzymes (DUBs) can reverse the effect of E3 ligases by the removal of ubiquitin from substrate proteins, thus maintaining the protein quality control and homeostasis in the cell. The dysfunction or dysregulation of these multi-step reactions is closely related to pathogenic conditions; therefore, understanding the role of ubiquitination in diseases is highly valuable for therapeutic approaches. In this review, we first provide an overview of the molecular mechanism of ubiquitination and UPS; then, we attempt to summarize the most common diseases affecting the dysfunction or dysregulation of these mechanisms. MDPI 2020-09-01 /pmc/articles/PMC7503467/ /pubmed/32882786 http://dx.doi.org/10.3390/ijms21176335 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Celebi, Gizem
Kesim, Hale
Ozer, Ebru
Kutlu, Ozlem
The Effect of Dysfunctional Ubiquitin Enzymes in the Pathogenesis of Most Common Diseases
title The Effect of Dysfunctional Ubiquitin Enzymes in the Pathogenesis of Most Common Diseases
title_full The Effect of Dysfunctional Ubiquitin Enzymes in the Pathogenesis of Most Common Diseases
title_fullStr The Effect of Dysfunctional Ubiquitin Enzymes in the Pathogenesis of Most Common Diseases
title_full_unstemmed The Effect of Dysfunctional Ubiquitin Enzymes in the Pathogenesis of Most Common Diseases
title_short The Effect of Dysfunctional Ubiquitin Enzymes in the Pathogenesis of Most Common Diseases
title_sort effect of dysfunctional ubiquitin enzymes in the pathogenesis of most common diseases
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7503467/
https://www.ncbi.nlm.nih.gov/pubmed/32882786
http://dx.doi.org/10.3390/ijms21176335
work_keys_str_mv AT celebigizem theeffectofdysfunctionalubiquitinenzymesinthepathogenesisofmostcommondiseases
AT kesimhale theeffectofdysfunctionalubiquitinenzymesinthepathogenesisofmostcommondiseases
AT ozerebru theeffectofdysfunctionalubiquitinenzymesinthepathogenesisofmostcommondiseases
AT kutluozlem theeffectofdysfunctionalubiquitinenzymesinthepathogenesisofmostcommondiseases
AT celebigizem effectofdysfunctionalubiquitinenzymesinthepathogenesisofmostcommondiseases
AT kesimhale effectofdysfunctionalubiquitinenzymesinthepathogenesisofmostcommondiseases
AT ozerebru effectofdysfunctionalubiquitinenzymesinthepathogenesisofmostcommondiseases
AT kutluozlem effectofdysfunctionalubiquitinenzymesinthepathogenesisofmostcommondiseases